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Sex differences in gene expression with galactosylceramide treatment in Cln3(Δex7/8) mice

BACKGROUND: CLN3 disease is caused by mutations in the CLN3 gene. The purpose of this study is to discern global expression patterns reflecting therapeutic targets in CLN3 disease. METHODS: Differential gene expression in vehicle-exposed mouse brain was determined after intraperitoneal vehicle/Galac...

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Detalles Bibliográficos
Autores principales: Makoukji, Joelle, El-Sitt, Sally, Makhoul, Nadine J., Soueid, Jihane, Kadara, Humam, Boustany, Rose-Mary
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7531864/
https://www.ncbi.nlm.nih.gov/pubmed/33006978
http://dx.doi.org/10.1371/journal.pone.0239537
Descripción
Sumario:BACKGROUND: CLN3 disease is caused by mutations in the CLN3 gene. The purpose of this study is to discern global expression patterns reflecting therapeutic targets in CLN3 disease. METHODS: Differential gene expression in vehicle-exposed mouse brain was determined after intraperitoneal vehicle/Galactosylceramide (GalCer) injections for 40 weeks with GeneChip Mouse Genome 430 2.0 arrays. RESULTS: Analysis identified 66 genes in male and 30 in female brains differentially expressed in GalCer-treated versus vehicle-exposed Cln3(Δex7/8) mice. Gene ontology revealed aberrations of biological function including developmental, cellular, and behavioral processes. GalCer treatment altered pathways of long-term potentiation/depression, estrogen signaling, synaptic vesicle cycle, ErbB signaling, and prion diseases in males, but prolactin signaling, selenium compound metabolism and steroid biosynthesis in females. Gene-gene network analysis highlighted networks functionally pertinent to GalCer treatment encompassing motor dysfunction, neurodegeneration, memory disorder, inflammation and astrogliosis in males, and, cataracts, inflammation, astrogliosis, and anxiety in females. CONCLUSIONS: This study sheds light on global expression patterns following GalCer treatment of Cln3(Δex7/8) mice. Understanding molecular effects of GalCer on mouse brain gene expression, paves the way for personalized strategies for treating this debilitating disease in humans.